Utility of Liquid Biopsy (CTCs) after Liver Transplantation in Cirrhotic Patients with Hepatocarcinoma

Abstract

Introduction New markers associated with angiogenesis and tumor metastasis, such as circulating tumor cells (CTCs), are opening up new avenues in cancer management from the laboratory. The Aim of this work is to determine the number of CTCs in patients included in waiting list for liver transplantation of hepatocellular carcinoma and to study its possible association with the alpha fetoprotein tumor marker (AFP) and with clinical variables such as number of tumors, presence of tumor vascular invasion, waiting list time, time from diagnosis and post-transplant tumor recurrence. In addition, we intend to compare the pre-transplant levels of CTCs with those obtained one month, six months, one year and two years after the transplant. Materials and Methods Peripheral blood of 36 patients suffering hepatocellular carcinoma once included in waiting list for liver transplant was obtained. 29 of them were transplanted, 27 of whom had blood extracted one month after the transplant, 19 of them after 6 months and one year after the transplant and 11 of them two years after the transplant. In order to study the correlation between the concentration of CTCs and the concentration of AFP, number of tumors, time on waiting list and from diagnosis in the patients, the Rho Spearman test was used. The study of the association of the CTCs levels with vascular invasion and presence of post-transplant recurrence was conducted with Mann-Whitney U test. For the variation in the levels of CTCs before and after the transplant, the Wilcoxon (SPSS 15.0) test was used. Results The average concentration of CTCs in the 36 patients before transplant was 11.50 CTCs/10mL (RI=2.25-42). A statistically significant positive correlation was found between the pre-transplant levels of CTCs and the days on waiting list (Rho= 0,376 p=0,024). The CTCs were not correlated in a significant way with the AFP concentration, number of tumors and time since diagnosis. (p>0,05). Out of the 29 transplanted patients, 2 showed vascular invasion in liver. Differences in the levels of CTCs were found between the patients with and without vascular invasion (U=0,00 p=0,020), these being significantly higher in the patients with vascular invasion. However, no significant differences were found in the levels of CTCs of the patients with recurrence after transplantation (4 patients) as opposed to those who didn’t (U=42 p=0.611). Conclusions Our conclusion is that the levels of tumor cells in peripheral blood could be an unfavourable prognostic factor associated to longer waiting times and to the presence of vascular invasion by tumor with an increased risk of relapse and post-transplant metastasis. In addition, we can see how their levels decrease significantly after transplantation. However, it would be necessary to increase the number of patients in the study, as well as the follow-up time, in order to achieve greater clinical evidence for its utility.